scholarly journals Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Virginia Rivulgo ◽  
Mónica Sparo ◽  
Mónica Ceci ◽  
Elida Fumuso ◽  
Alejandra Confalonieri ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Lung Tissue ◽  
Murine Model ◽  
Tissue Concentration ◽  
Preclinical Study ◽  
Therapeutic Failure ◽  
Pharmacokinetic Analysis ◽  
Tissue Samples ◽  
Group A ◽  
Group B

Azithromycin (AZM) therapeutic failure and relapses of patients treated with generic formulations have been observed in clinical practice. The main goal of this research was to compare in a preclinical study the serum exposure and lung tissue concentration of two commercial formulations AZM-based in murine model. The current study involved 264 healthy Balb-C. Mice were divided into two groups (n=44): animals of Group A (reference formulation -R-) were orally treated with AZM suspension at 10 mg/kg of b.w. Experimental animals of Group B (generic formulation -G-) received identical treatment than Group A with a generic formulation AZM-based. The study was repeated twice as Phase II and III. Serum and lung tissue samples were taken 24 h post treatment. Validated microbiological assay was used to determine the serum pharmacokinetic and lung distribution of AZM. After the pharmacokinetic analysis was observed, a similar serum exposure for both formulations of AZM assayed. In contrast, statistical differences (P<0.001) were obtained after comparing the concentrations of both formulations in lung tissue, being the values obtained for AUC and Cmax (AZM-R-) +1586 and 122%, respectively, than those obtained for AZM-G- in lung. These differences may indicate large differences on the distribution process of both formulations, which may explain the lack of efficacy/therapeutic failure observed on clinical practice.

Histopathologic lesions in conventional pigs experimentally infected with Haemophilus parasuis serovar 5

2015 ◽  
Vol 43 (02) ◽  
pp. 91-96 ◽  
Author(s):  
R.-L. Austin-Busse ◽  
A. Ladinig ◽  
G. Balka ◽  
S. Zoels ◽  
M. Ritzmann ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Control Group ◽  
Post Inoculation ◽  
Haemophilus Parasuis ◽  
Tissue Samples ◽  
Group A ◽  
Pathologic Lesions ◽  
Group B ◽  
Kidney Lesions ◽  
Challenge Group

Summary Objective: In the present study various tissues of pigs were investigated for the presence of histopathologic lesions after an experimental infection with Haemophilus (H.) parasuis serovar 5. Material and methods: Conventional pigs (n = 36) were divided into a control group B (n = 9) and a challenge group A (n = 27), which was infected intratracheally. Pigs that did not die prior to study termination were euthanized on day 14 post inoculation. Postmortem samples of the lung, heart, liver, kidney, spleen, left tarsal joint capsule and brain were collected. Results: All but one pig with detectable histopathologic lesions (n = 11) showed typical macroscopic changes. Histopatho logic examination of all tissue samples identified pyelitis (n = 10), synovitis (n = 7) and meningitis (n = 7) and all those animals were euthanized prior to study termination. No histopathologic lesions were found in pigs of the control group. The correlations between pyelitis and meningitis, pyelitis and synovitis and synovitis and meningitis were significant (p < 0.001). No significant correlation could be observed between the histopathologic and the clinical examination of the joints. The investigation of samples from the joints by PCR was not significantly correlated with the observed synovitis. The clinical observation of neurologic signs was significantly correlated with meningitis (p = 0.03). A significant correlation (p < 0.001) could be detected between meningitis and the detection of H. parasuis by PCR in brain samples. Conclusions: H. parasuis constantly causes clinical signs and pathologic lesions as soon as it infects the brain while it can infect the joints without causing histopathologic lesions. Pigs with histopathologic lesions do not always show typical clinical signs. Only few studies described the finding of kidney lesions in pigs with Glässer’s disease and this is the first study to describe a pyelitis in pigs experimentally infected with H. parasuis. The observed pyelitis mainly occurred in acute cases.

scholarly journals Effect of Naoxintong Capsules on the Activities of CYP450 and Metabolism of Metoprolol Tartrate in Rats Evaluated by Probe Cocktail and Pharmacokinetic Methods

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Huizi Ouyang ◽  
Jiayuan Shen ◽  
Xuhua Huang ◽  
Wenjuan Ma ◽  
Qi Jia ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Drug Treatment ◽  
Drug Interactions ◽  
Rat Plasma ◽  
Therapeutic Failure ◽  
Metoprolol Tartrate ◽  
Conventional Drug ◽  
Group A ◽  
Group B ◽  
Opposite Tendency

Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe drugs, namely, omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) to study the potential influences of NXT on the activities of CYP enzymes and assessed the pharmacokinetics effect of NXT on metoprolol tartrate in rat plasma. The study showed that AUC(0–24) and AUC(0–∞) of midazolam (CYP3A4) in NXT coadministration group (283.7 ± 65.2 h·ng·mL−1 and 292.0 ± 75.1 h·ng·mL−1 in group B; 295.7 ± 62.7 h·ng·mL−1 and 299.5 ± 60.0 h·ng·mL−1 in group C) were significantly decreased as compared to another group (416.8 ± 82.3 h·ng·mL−1 and 424.9 ± 77.9 h·ng·mL−1 in group A), while that of dextromethorphan (CYP2D6) showed an opposite tendency (540.7 ± 119.7 h·ng·mL−1 and 595.3 ± 122.2 h·ng·mL−1 in group A, 760.6 ± 184.9 h·ng·mL−1 and 788.7 ± 211.0 h·ng·mL−1 in group B, and 734.3 ± 118.5 h·ng·mL−1 and 757.2 ± 105.4 h·ng·mL−1 in group C). Moreover, NXT preadministration can enhance the metabolism of metoprolol tartrate and reduce the metabolism of O-demethylmetoprolol. The results indicated that NXT had potential effects in inducing CYP3A4 and inhibiting CYP2D6 in the metabolism of metoprolol tartrate. It suggests that patients who coadministered NXT and metoprolol tartrate should be advised of potential herb-drug interactions (HDIs) to reduce therapeutic failure or accelerated toxicity of conventional drug treatment.

scholarly journals Pathological and microbiological impact of a gentamicin-loaded biocomposite following limited or extensive debridement in a porcine model of osteomyelitis

2020 ◽  
Vol 9 (7) ◽  
pp. 394-401
Author(s):  
Sophie A. Blirup-Plum ◽  
Thomas Bjarnsholt ◽  
Henrik E. Jensen ◽  
Kasper N. Kragh ◽  
Bent Aalbæk ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Porcine Model ◽  
Drill Hole ◽  
Post Mortem ◽  
Tissue Samples ◽  
Group A ◽  
Extensive Debridement ◽  
Group B ◽  
The Right ◽  
Surrounding Bone

Aims CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401.

Should liver metastases of breast cancer be biopsied to improve treatment choice?

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA1008-CRA1008 ◽  
Author(s):  
M. A. Locatelli ◽  
G. Curigliano ◽  
L. Fumagalli ◽  
V. Bagnardi ◽  
G. Aurilio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Treatment Choice ◽  
Her2 Status ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Er Positive ◽  
Group A ◽  
Group B

CRA1008 Background: Decision making on systemic treatment of women with metastatic breast cancer is based on features like estrogen receptor (ER), progesterone receptor (PgR), and HER2 status assessed on the primary tumor. We evaluated the concordance of receptor status between primary tumor and liver metastases (mts) and its impact on treatment choice. Methods: We retrospectively analyzed a database including ultrasound guided liver biopsies performed from 1995 to 2008. All tissue samples, both from primary tumor and liver mts, were analyzed for ER, PgR and HER2 status. Clinical and biological data were obtained from medical charts. Differences between proportions were evaluated using the Pearson chi-square test. Results: We identified 255 consecutive patients (pts) with matched primary and liver tissue samples. Median time from primary diagnosis to liver biopsy was 3.4 years (range 0-18.3 years). Changes in ER status were observed in 41/255 pts (16.0%). 16/58 pts (27.6%) changed from ER-negative to ER-positive and 25/197 pts (12.7%) changed from ER-positive to ER-negative (p=0.0066). Changes in PgR status were observed in 76/255 pts (29.8%). 18/91 pts (19.8%) changed from PgR-negative to -positive and 58/164 pts (64.6%) from PgR-positive to PgR-negative (p <0.0001). 12/52 pts (23.1%) changed from ER- and PgR-negative to ER- or PgR-positive (group A) and 27/203 pts (13.3%) changed from ER- or PgR-positive to ER- and PgR-negative (group B) (p=0.087). In the group A the treatment of 4/12 pts (33.3%) was changed after biopsy: 2/4 started endocrine treatment (HT) and 2/4 stopped it. In group B the treatment of 18/27 pts (66.6%) was changed after biopsy: 17/18 stopped HT. Changes in HER2 status were observed in 22/167 pts (13.1%): 6/116 pts (5.1%) changed from HER2-negative to HER2-positive and 16/51 pts (31.4%) changed from HER2-positive to negative (p≤0.0001). In this group pts started and/or stopped a trastuzumab containing treatment after biopsy. Conclusions: There was a discordance in receptor status between primary tumor and liver mts, which led to change in therapy for 48/255 of pts (18.8%). Biopsy of metastases for reassessment of biological features should be considered in all pts when safe and easy to perform, since it is likely to impact treatment choice. No significant financial relationships to disclose.

Transcriptional characterization of microenvironment and their prediction role for the prognosis of hepatocellular carcinoma after surgery.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15650-e15650
Author(s):  
Kehe Chen ◽  
Haiming Wei ◽  
Tianqi Liu ◽  
Zhenxiang Chen ◽  
Deng Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Antigen Processing ◽  
Tissue Samples ◽  
Ffpe Tumor ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Immune Related Genes ◽  
The Impact

e15650 Background: Hepatocellular carcinoma (HCC) is one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with HCC, surgical treatment is a potentially cutative therapy. However, the puzzle in the therapy was the rapid recurrence after surgery. The purpose of this study was to integrate the impact of different immune context present in HCC microenvironment on patients’ prognosis, provide the molecular prediction clue of HCC recurrence. Methods: RNA targeted sequencing was performed on 12 primary tumor specimens from HCC patients. Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The lima package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the recurrence post-resection. Results: 15 DEGs were detected in tissue samples between the two groups (group A: patients who relapsed within one year after surgery; group B: patients who hadn't relapsed beyond two years after surgery). The Antigen processing pathway enrichment may associate with the favorable prognosis (p < 0.05). HLA-A gene expression in group A was lower than that in group B; The gene expression of IL23A, TP63, ALOX15B, BUB1, CXCR2, CCL20, CLEC4C, PTK7, MPO, IL1B, MMP9, GAGE2C, GAGE2A, GAGE2E, DMBT1, FOXM1 in group A was higher than that in group B. Additionally, the combination of 3 genes (TP63, IL23A and BUB1) can distinguish the patients recurrent within 1 year or beyond 2 years post-resection. The joint diagnostic equation is logit (Y = 1) = 0.073 +0.740 *(TP63) + 0.589 * (IL23A)+0.959(BUB1), (Optimal threshold: 0.667, specificity: 1, sensitivity: 0.833). Conclusions: Our results suggest that RNA-seq of immune related genes from FFPE sample can effectively profile the specific landscape of tumor immune microenvironment and predict the survival of HCC. 3 genes’ expression (TP63, IL23A and BUB1) might correlate with recurrence in HCC patients after surgery.

scholarly journals Modern critical approach to the diagnosis of acute viral myocarditis and inflammatory cardiomyopathies in clinical practice: Focus on the roles of echocardiography and antivirus antibodies

2021 ◽  
Vol 46 (2) ◽  
pp. 57-71
Author(s):  
Dušan Bastać ◽  
Biserka Tirmenštajn-Janković ◽  
Predrag Marušić ◽  
Zoran Joksimović ◽  
Vojkan Čvorović ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Diastolic Function ◽  
Viral Myocarditis ◽  
Left Ventricular ◽  
Control Group ◽  
Acute Viral Myocarditis ◽  
Significant Difference ◽  
Echocardiographic Parameters ◽  
Group A ◽  
Group B

SIGNIFICANCE OF THE PROBLEM: The diagnosis of acute viral myocarditis is one of the diagnoses most difficult to make in cardiology and medicine in general. Echocardiography and cardiomagnetic resonance play a crucial role in the clinical diagnosis and the serum titer of antiviral antibodies to cardiotropic viruses is still unjustifiably used for the diagnosis of myocarditis in everyday practice. RESEARCH OBJECTIVES: To analyze the frequency and significance of echocardiographic parameters in the diagnosis of clinically suspected acute viral myocarditis, to determine the role of antiviral antibody titer (AVA) dynamics for the diagnosis of myocarditis and to compare viral serology and echocardiographic function versus echocardiographic function. METHODOLOGY: A retrograde transverse study was performed in the ten-year period from 2006. to 2015, where 126 consecutive patients from the database of the Office of Internal medicine ''Dr. Bastać'' were analyzed, with a working diagnosis of clinically suspected viral myocarditis. They were clinically, ECG, echocardiographically and serologically monitored for 4 to 8 weeks due to the dynamics of AVA titer. The examined group (A) was divided into subgroups: A1 with elevated AVA class IgM titer in 43 (32%) subjects and subgroup A2 without elevated IgM titer in 83 (68%) patients. The control group of healthy (B) of 103 subjects was comparable.Statistical processing was done in the EXCELL database via descriptive statistics, Student's-T test and Chi2 test. RESULTS: 126 patients had clinically suspected myocarditis (≥2 ESC criteria). Diastolic left ventricular dysfunction in 39/126 (31%) patients was the dominant echocardiographic criterion for clinically suspected myocarditis. Reduced ejection fraction (EF <50%) was measured at 19/126 (15%), followed by left ventricular dilatation. Regional systolic dysfunction was found in 21/126 (17%) and changes in myocardial texture in 17 (13%) subjects. The clinical probability of viral etiology was diagnostically supported by elevated titer of IgM antibodies in 43 (32%) subjects (subgroup A1) where IgM antibodies to Parvo B 19 virus predominate in 36/43 patients (84%). Most were without elevated titer of IgM antibodysubgroup A2 83 (68%). Clear dynamics of IgM antibody titer was observed in 23 persons, a decrease in IgM titer with an increase in IgG titer (seroconversion) in 13 patients. Determination of anti-heart autoantibodies (AHA) was done in 17 severe cases, of which 9 had positive AHA. A comparison of subgroups A1 and A2 did not reveal a statistically significant difference in echocardiographic parameters. The whole group A of clinically suspected myocarditis compared to control group B has statistically highly significantly lower parameters of global systolic (EF=8,7±4,6 vs. 63±7,9; p<0,001), longitudinal systolic (S'=6,9±1,3 vs. 9,9±2,1) and diastolic function (E/e'11,9±4,8 vs. 8,7±4,6; p<0,001), and a highly statistically significant increase in left ventricular telediastolic dimension, myocardial mass index, and left atrial size. CONCLUSION: The diagnosis of acute viral myocarditis in clinical practice is made on the basis of the clinical picture, ECG and echocardiography that indicate myocarditis with the exclusion of cardiac comorbidities, based on the ESC criteria for suspected clinical myocarditis. The whole group A had highly statistically significantly lower parameters of systolic and diastolic function compared to control group B. Normal ECG and echocardiography cannot serve to exclude the diagnosis of myocarditis. Comparison of subgroups A1 and A2 did not reveal a statistically significant difference in echocardiographic parameters.

scholarly journals Integration of CTA in the Diagnostic Workup of New Onset Chest Pain in Clinical Practice

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Nazario Carrabba ◽  
Martina Berteotti ◽  
Giulia Taborchi ◽  
Francesca Ciatti ◽  
Manlio Acquafresca ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Chest Pain ◽  
Diagnostic Workup ◽  
Second Line ◽  
Functional Tests ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
New Onset

Background. Recently, NICE guidelines recommend the use of computed tomographic angiography (CTA) as the first line of investigation for new onset chest pain. We sought to evaluate the impact of the integration of CTA in the diagnostic workup, as either a first- or second-line of investigation, in the clinical practice for patients presenting with new onset chest pain, with suspicion that it may be due to coronary artery disease (CAD). Method and Results. From 2014 to 2016, 208 outpatients (mean age 63.8 ± 12.7, 37% female) with an unknown CAD diagnosis were evaluated. About half (n=106, 51%) received usual testing care plus CTA as a second-line investigation (group A), while the other half (n=102, 49%) received CTA as a first-line investigation (group B). Care decisions and test interpretations were made by the attending physician. Obstructive CAD (O-CAD) was defined as >50% stenosis in the principal branch. As determined by CTA, the rates of CAD in group A vs. group B were the following (P=0.001): 31.1% vs. 27.4% for normal/minimal CAD; 42.5% vs. 63.7% for no O-CAD; and 26.4% vs. 8.8% with O-CAD. Based on a diagnostic result of no O-CAD, invasive angiography was cancelled in 42.6% (n=45) of group A patients, and additional functional tests were cancelled for the same reason in 63.7% (n=65) of group B patients, without adverse events at median 3-year. The average diagnostic cost for patients in our study was lower in group B (206 vs. 324.42 euro; P<0.0001). Conclusions. In clinical practice, CTA, as a first- or second-line investigation, most commonly detected no O-CAD in new onset chest pain patients, leading us to safely avoid unnecessary ICA or additional functional tests. The use of CTA as a first-line investigation also appears to be cost saving, but its cost-effectiveness remains to be demonstrated in larger studies.

Is cancer associated thrombosis (CAT) an underestimated issue in oncology clinical practice? Real-world data regarding long term management of CAT.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23150-e23150
Author(s):  
Nikolaos Tsoukalas ◽  
Alexandros Bokas ◽  
Evangelos Bournakis ◽  
Athina Christopoulou ◽  
Christos Papandreou ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Natural History ◽  
Disease Stage ◽  
Lower Probability ◽  
Bleeding Events ◽  
History Of ◽  
Group A ◽  
Group B ◽  
History Of Cancer

e23150 Background: Cancer is associated with thrombosis due to different pathophysiological processes. CAT is the 2nd cause of death in oncology patients and can occur anytime during the natural history of cancer. CAT is not rare complication, can delay anti-cancer therapy and increase health systems costs. Methods: A prospective observational study (Greek Management of Thrombosis-GMaT) conducted by HeSMO in Greek Oncology units for two years aiming to record clinical practice of CAT management. Patients with active cancer who received CAT treatment or thromboprophylaxis were enrolled after signing informed consent. Results: 546 patients were enrolled from 18 oncology units. Primary cancers were: lung 23.9%, pancreas 13.3%, breast 7.6%, colorectal 8.9%, stomach 8.3%, ovarian 7.6% and other 30.5%. 120 patients received LMWH for Venus Thombo-Embolism (VTE) treatment (Group A) and 426 for thromboprophylaxis (Group B). Group A: 89/120 (74.17%) patients continued in 2nd year and 58.6% received CAT treatment (6.9±4.4 months). Only 2 had VTE recurrence in 2nd year (versus 3 in 1st year). 4/120 (3.33%) had bleeding events (grade 1) in 1st year while no bleeding events occurred in 2nd year. Group B: 345/426 (80.98%) patients continued in 2nd year. 126 (30%) had Khorana score ≥3 and 300 (70%) had Khorana score ≤2. In 2nd year, 123 (35.65%) received thromboprophylaxis (7.3±3.7 months) while 79.4% of them were initially treated with High Thrombotic Treatment Agents (HTTA: e.g. platinum, 5-FU) and 83.1% had metastatic disease. In 2nd year, 52.5% received LMWHs at prophylactic dose and 47.5% at therapeutic dose. Overall, 12 (2.82%) had thrombotic events whereas 4 were recorded in 2nd year. Notably, patients treated with therapeutic doses had lower probability to have a thrombotic event (OR: 5.8, 95% CI: 1.7 to 20.5, p < .05). Six (1.41%) bleeding events (grade 1) occurred in 1st year and one (0.81%) in 2nd year. Conclusions: LMWHs can be used for long term CAT management. Therapeutic LMWHs doses as thromboprophylaxis are safe and effective. Khorana score is a useful model for CAT risk assessment but some other factors such as disease stage and HTTA might be taken into account. CAT can occur anytime during the natural history of cancer. Oncologists should be aware about CAT and its negative influences in patients’ prognosis and quality of life.

Adoption of patient-reported outcomes (PROs) in clinical practice for older patients receiving active anticancer treatment: Impact on health-related quality of life (QoL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24014-e24014
Author(s):  
Clizia Zichi ◽  
Elisa Sperti ◽  
Donatella Marino ◽  
Gaetano Lacidogna ◽  
Francesca Vignani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cancer Treatment ◽  
Effect Size ◽  
Older Patients ◽  
Secondary Analysis ◽  
Patient Reported ◽  
Anti Cancer ◽  
Anticancer Treatment ◽  
Group A ◽  
Group B

e24014 Background: PROs are the gold standard to describe subjective symptoms. In order to improve clinical management of outpatients receiving active anti-cancer treatment at Medical Oncology, Mauriziano Hospital, Turin, Italy, in January 2018 we introduced in routine clinical practice an assessment of patient-reported symptoms and toxicities. We demonstrated that use of PROs in clinical practice was associated with a significant QoL improvement, compared to the traditional visit (Baratelli, Support Care Cancer 2019). In this secondary analysis, we show the results obtained in older pts ( > 70yrs). Methods: Eligible pts were receiving an active anti-cancer treatment, as outpatients. Pts treated in 2017 underwent “usual” visits (group A), while pts treated in 2018 before each visit received a paper questionnaire by a dedicated nurse, in order to provide information about symptoms and toxicities to be discussed during visit (group B). Primary objective was the comparison of QoL changes, measured by EORTC QLQ-C30. Results: Out of 211 pts, 88 were older than 70 yrs (47 group A, 41 group B). Median age was 76 (70-84 yrs). Most common tumors were colorectal (25.0%), lung (22.7%) and pancreatic (17.0%). 68.2% were receiving first-line treatment. Tumors and setting were similar between group A and B. Younger and older pts had comparable baseline QoL scores: mean global QoL score was 59.96 in younger pts vs. 57.39 in older pts. After 1 month, global QoL of older pts was significantly improved in group B compared to group A: mean change from baseline was -0.89 group A vs. +4.47 group B (p = 0.006, effect size 0.23). There were statistically significant differences in mean changes from baseline, in favor of group B, for role functioning (-5.67 group A and -0.81 group B, p = 0.034, effect size 0.20) and emotional functioning (-2.30 group A and +3.25 group B, p = 0.014, effect size 0.36). Mean changes from baseline for pain were significantly better for group B (-3.25) than group A (+6.03, p = 0.01, effect size 0.43). There were no significant differences between the 2 groups in terms of other functional scales or symptoms. There was no significant heterogeneity in the proportion of QoL responders between younger and older pts (p = 0.60). The proportion of older pts obtaining a clinically significant improvement in global QoL was numerically higher in group B (36.6%) compared to group A (19.1%, p = 0.09). Odds Ratio of obtaining an improvement in global QoL for group B vs group A was 1.73 (95%CI 0.75 – 3.99) in younger pts and 2.44 (95%CI 0.93 – 6.40) in older pts. Conclusions: This secondary analysis shows that the use of PROs in clinical practice, thanks to an active role of nurses and discussion of symptoms with physicians during the visit, is associated, also in older patients receiving active anticancer treatment, with a significant improvement in global QoL.

Effectiveness of Various Dosage Regimens of Azacitidine In Patients with Myelodysplastic Syndromes: Safety and Efficacy Final Data From the Spanish Azacitidine Compassionate Use Registry

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1853-1853 ◽  
Author(s):  
Regina García ◽  
Dunia De Miguel ◽  
Joan Bargay ◽  
Teresa Bernal ◽  
José Ramón Gonzalez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Dosage Regimen ◽  
Performance Status ◽  
Routine Clinical Practice ◽  
Compassionate Use ◽  
Care Environment ◽  
Dosage Regimens ◽  
Group A ◽  
Group B

Abstract Abstract 1853 Introduction: Azacitidine (AZA), an hypomethylating agent approved in Europe for the treatment of MDS, prolongs the median survival time of patients included in clinical trials (Fenaux et al., 2009). AZA was available for clinical trials or compassionate use in Spain before receiving marketing authorization in Spain in May 2009. The dosage regimen of AZA in routine clinical practice (not in clinical trials) may have been adapted to the care environment at each center. We hereby present the results of the final analysis from a longitudinal, multicenter Spanish patient registry. Materials and Methods: This analysis retrospectively gathers clinical data about the treatment and disease progression of patients with MDS who had received AZA in compassionate use conditions, and for whom the dosage regimen was documented. AZA doses were administered to patients in three different dosage regimens at the beginning of each 28-day cycle; group A: days 1–5 (M-F)/group B: days 1–5, 8–9 (M-F, M-Tu)/group C: days 1–7 (M-Su). Patients who received an initial dose other than 75mg/m2 were excluded from this analysis. Treatment assignment was based on the patient's condition and on the viability of the care environment for drug administration during weekends. Treatment effectiveness and tolerance were analyzed based on the patients’ basal conditions, stratified by the dosage schedule. Results: Data were collected from 181 patients with MDS according to the WHO diagnostic criteria. Their demographic characteristics were similar at the beginning of the study, except for their ECOG performance status, with a statistically-significant higher prevalence of an ECOG ≥ 2 in the administration group C (table 1). The three dosage regimens of AZA were applied in the following proportions: group A 32.3%, group B 27.5% and group C 36.5%. The median number of administered cycles was similar for all groups (6 cycles). The overall response rates for the treatment (IWG 2006 criteria) were as follows: group A 38%, group B 71% and group C 52% (p group A vs. B=0.0005, p group A vs. C=0.0982, p group B vs. C =0.0418). No differences were observed in survival between chromosome 7 abnormalities and an intermediate abnormal karyotype (HR 1.11; p=0.83). AZA treatment was well tolerated. Most of the adverse events were hematological. The adverse event profile varied based on the dose regimen group (Table). Conclusions: The data of the 181 patients evaluated shows that in routine clinical practice effectiveness and tolerance differ when different dosage regimens are used. A better effectiveness/tolerance profile is observed in those regimens with a lower period of time to next cycle. Disclosures: García: Celgene : Research Funding.

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